According to the devs, if you delete a key in Sbie, it will be deleted --> not read from host.
If you clear the sandbox, it will be read from host instead. Are you clearing the contents of your Sandbox?

In order to test this behavior I need to know what are you doing, exactly.
Please provide repro steps, include any workspaces you may be using, changes you are looking at, and how are you resetting the application.

Install EmEditor (Installer version, which will use the registry).
Run EmEditor outside (with default settings). Change its window size/position.
(Restart EmEditor. It should use the changed size/position.)

Run EmEditor in a sandbox.
Use the menu: Tools > All Commands.
Then in the (All Commands) popup menu: Tools > Reset All Settings.
Follow the prompts.

After restarted, EmEditor should use the default window size/position (if you don't have my issue).

I see the behavior. The window size is still remembered, even after using "Reset all settings".
I have made the devs aware.

As a workaround you can add the following entry under the desired Sandbox:
Open Sandboxie Control
Configure --- > Edit configuration
Find the Sandbox you wish to modify and add this at the end:
WriteKeyPath=HKEY_CURRENT_USER\Software\EmSoft

However, in a Sandboxie sandbox, EmEditor can never reset its registry settings. When restarted, it uses the old window size and position, for example.

This is the expected behaviour. Sandboxie not only keeps copies of changed files inside of the sandbox, unless an exclusion setting allows them out, but it also keeps registry changes confined to the sandbox - unless an exclusion is set at:
Sandbox Settings > Resource Access > Registry Access
I would use "Direct Access" (OpenKeyPath).
Look at templates.ini in Sandboxie's Program Files folder, and you will see plenty of OpenKeyPath settings used in the pre-defined templates.

Registry changes for the sandboxed program are kept in the Reghive files, inside of the sandbox. So any Registry changes that are made by the sandboxed program stays in those files, and is deleted when the sandbox contents are deleted.
The Reghive is mounted to the "real" Registry whenever the sandbox is in use, and dismounted when the sandbox is not in use.

You can examine the Registry changes by using the Registry Editor (regedit.exe) while the sandbox is in use, at:
HKEY_USERS\Sandbox_...

We cannot repro the IE behavior. After setting it to Default and re-launching it inside Sbie, the button is grayed out.
Be sure that your sandbox is not set to delete contents when you close an app , and then re-try (if possible, please test in a new sandbox with default settings).
Please let us know the outcome.